CXCL12 expression is an adverse predictor for disease recurrence in patients with metastatic non-seminomatous testicular germ cell tumors.

To validate the utility of the chemokine ligand 12 (CXCL12) as prognostic marker in patients with localized and metastatic germ cell tumors (GCT).

CXCL12 expression was analyzed on a tissue microarray consisting of 750 tissue cores of different histological tumor components, Germ cell neoplasia in situ (GCNIS) and adjacent normal tissue of 263 testicular cancer patients using a semi-quantitative score. The association between CXCL12 expression and recurrence-free survival (RFS) as well as overall survival (OS) was assessed using Kaplan-Meier curves with log-rank tests.

CXCL12 expression was absent in all seminomas but was found in 52 of 99 (52.5%) non-seminomas. Follow-up was available for 260 patients of which 36 (13.8%) recurred. In patients with stage 1 non-seminoma GCT, CXCL12 expression was not associated with higher risk of disease recurrence (p = 0.270). In contrast, post chemotherapy RFS of patients with metastatic non-seminoma and positive CXCL12 expression was significantly shorter compared to CXCL12 negative patients (p = 0.003). OS differences were not statistically different between patients with CXCL12 positive or negative tumors for either localized or metastatic disease.

CXCL12 is almost exclusively expressed in non-seminoma. Pure seminoma, GCNIS and adjacent normal testicular tissue are CXCL12 negative. Our analysis suggests that patients with metastatic disease and a CXCL12-positive non-seminoma are at higher risk for disease recurrence after first-line chemotherapy and might thus be candidates for more intensive treatment and/or closer follow-up.

BMC cancer. 2019 Aug 14*** epublish ***

Christian Daniel Fankhauser, Lisa Roth, Nico Christian Grossmann, Benedikt Kranzbühler, Daniel Eberli, Tullio Sulser, Holger Moch, Peter-Karl Bode, Joerg Beyer, Thomas Hermanns

Department of Urology, University Hospital, University of Zurich, Zurich, Switzerland. ., Department of Urology, University Hospital, University of Zurich, Zurich, Switzerland., Department of Pathology of Molecular Pathology, University Hospital, University of Zurich, Zurich, Switzerland., Department of Oncology, University Hospital, University of Bern, Bern, Switzerland.